Substituted pyrazolo{8 4,3-c{9 pyridine compounds

ABSTRACT

PYRIDYL, THIENYL OR FURYL; R is hydrogen, alkyl of 1 to 4 carbons, hydroxy-alkyl of 1 to 4 carbons, alkanoyl of 2 to 5 carbons, or   D R A W I N G WHEREIN ALKYL IS OF 1 TO 3 CARBONS, N IS AN INTEGER FROM 1 TO 4; AND X, X1, X2 and X3 are independently selected from hydrogen, chlorine, fluorine, trifluoromethyl, alkyl of 1 to 4 carbons and alkoxy of 1 to 4 carbons; are disclosed. These compounds including their pharmaceutically acceptable acid-addition salts, quaternary ammonium salts, and N-oxides are useful as antimicrobial and antifungal agents.     WHEREIN R1 is alkyl of 1 to 4 carbons,   D R A W I N G Compounds of the formula

United States Patent [1 1 Krapcho et al.

[ Dec. 16, 1975 SUBSTITUTED PYRAZOLO[4,3-C]PYRIDINE COMPOUNDS [75] Inventors: John Krapcho, Somerset; Chester Frank Turk, Kendall Park, both of NJ.

[73] Assignee: E. R. Squibb & Sons, Inc.,

Princeton, NJ.

[22] Filed: Nov. 19, 1974 [21] Appl. No.: 525,148

[52] US. Cl 260/240 R; 260/293.55; 424/267 [51] Int. Cl. C07D 471/02 [58] Field of Search 260/293.55, 240 R [56] References Cited UNITED STATES PATENTS H1969 Blatler 260/293.55 X l/1974 Hoehn et al. 260/240 R X Primary Examiner-Allen B. Curtis Attorney, Agent, or Firm-Lawrence S. Levinson; Merle J. Smith; Stephen B. Davis [57] ABSTRACT Compounds of the formula pyridyl, thienyl or furyl; R is hydrogen, alkyl of l to 4 carbons, hydroxy-alkyl of l to 4 carbons, alkanoyl of 2 to 5 carbons, or

wherein alkyl is of 1 to 3 carbons, n is an integer from 1 to 4; and X, X, X and X are independently selected from hydrogen, chlorine, fluorine, trifluoromethyl, alkyl of l to 4 carbons and alkoxy of 1 to 4 carbons; are disclosed. These compounds including their pharmaceutically acceptable acid-addition salts, quaternary ammonium salts, and N-oxides are useful as antimicrobial and antifungal agents.

11 Claims, N0 Drawings SUBSTITUTED PYRAZOLO[ 4,3-C PYRIDINE COMPOUNDS SUMMARY OF THE INVENTION This invention relates to new compounds of the formula:

C X G and the pharmaceutically acceptable acid-addition salts, quaternary ammonium salts, and N-oxides thereof which have been'found to exhibit antimicrobial and antifungal activity when administered to mammalian species.

R represents alkyl of l to 4 carbons,

pyridyl, thienyl or furyl.

R represents hydrogen, alkyl of l to 4 carbons, alkanoyl of 2 to 5 carbons, hydroxy-alkyl of l to 4 carbons or Q-alkyl x i.e., acetyl, propionyl, etc.

The term acid addition salts is intended to mean salts which may be formed for the purposes of isolation, purification, and storage, such as the oxalate salt, picric salts, etc. and pharmaceutically acceptable salts meant for administration of the compound to a host, such as the hydrochloride, sulfate, acetate, maleate, citrate salts, etc.

The N-oxide may be formed by dissolving the free base of Formula I in a solvent inert to hydrogen peroxide, e.g.. ethanol or chloroform, adding excess (on a molar basis) hydrogen peroxide, and allowing the mixture to stand at room temperature for several hours. An acid-addition salt of the N-oxide may be formed by addition of the desired acid, for example, those mentioned above.

2 The quaternary ammonium salts include those formed with alkyl halides (e.g., methyl chloride, isobutyl bromide, dodecyl chloride and cetyl iodide), benzyl halides (e.g., benzyl chloride) and dilower alkyl sulfates (e.g., dimethyl sulfate).

DETAILED DESCRIPTION OF THE INVENTION The new compounds of formula I are prepared by reacting a pyrazolo[4,3-clpyridine of the formula R N N I 14 we 1 X f (II) H with a compound of the formula wherein halo is either chlorine or bromine. The reaction is performed in the presence of a suitable solvent such as benzene, toluene, ether, or dimethylformamide at a temperature of from about 20C to the reflux temperature of the solvent for from about 4 to about 24 hours, preferably from about 6 to about 20 hours.

When n is 2, it is preferred to prepare the compounds by reacting the compound of formula II with a vinyl ketone of the formula The vinyl ketone is available either directly as the compound of formula IV, i.e. where R is methyl one employs 3-buten-2-one, or as a compound which can be reacted so as to provide the ketone of formula IV, i.e. where R is phenyl one heats 3-(dimethylamino)-lphenyl- 1 -propanone which liberates The preparation of the pyrazolo[4,3-c1pyridine of formula II is disclosed in US. patent application Ser. No. 340,408, filed on Mar. 12, 1973.

As disclosed in that application, 4-piperidinone or preferably an N-acyl derivative thereof, eg the N- acetyl or N-benzoyl derivative, is reacted with an aldehyde of the formula utilizing the reaction procedure described in the Journal of the American Chemical Society, 70, I824 (1948) to give the compound of the formula o o X "X N By adjusting the ratio of reactants so as to have an excess of the 4-piperidinone present, compounds of the are prepared. Reacting the compound of the formula VI with an aldehyde of the formula in the manner described in the Journal of the American Chemical Society, 70, 1824 1948), gives a compound of the formula mail: GH

The compounds of formulae V and VII are generally isolated in the form of their acid addition salts.

The salts of the compounds of formulae V and VII, such as the hydrochloride salt, sulfate salt, phosphate salt, etc., are converted to a compound of formula II by reaction with a hydrazine of the formula H NNHR wherein R is hydrogen, alkyl, hydroxy-alkyl, or

alkyl BQ in a polar organic solvent, preferably an alcohol of up to four carbon atoms at temperatures of from about 40C to about 120C, preferably at about the reflux temperature of the solvent, for from about /2 to about 12 hours, preferably 4 hours.

Compounds of formula I wherein R is alkanoyl of from 2 to 5 carbons are prepared by acylating a compound of formula I wherein R is hydrogen with conventional acrylating agents of the formulae (VII) X, X, and X are independently selected from H, Cl, F, CF CH or OCH especially where X and X are the same.

Most preferred are the compounds of formula I wherein;

R is methyl.

R is methyl or X and X are the same and are selected from H, Cl, and F, especially where X and X are both hydrogen.

X is hydrogen, F, or Cl.

n is 2 or 3.

The new compounds of formula I are useful as antimicrobial and antifungal agents and may be used to combat infections in animal species, such as mice, rats, dogs, guinea pigs and the like, due to organisms such as Staphylococcus aureus, Escherichia coli, or Trichophyton mentawvp/zyles. For example, a compound or mixture of compounds of formula I or a pharmaceutically acceptable acid addition salt, N-oxide, or quaternary ammonium salt may be administered to the infected animal. In treating a microbial infection the compound may be administered orally in an amount ranging from about 5 to about 25 mg. per kg. per day in 2 to 4 divided doses. In particular, the compounds of formula I have been found to be effective in combating dermatophytes belonging to the genera Trichophyton, Microsporum, Epidermophyton, and Malassezia. For such dermophytic use the compounds are applied topically in a lotion, salve, or cream at a concentration of from about 0.01 to about 3.0 percent by weight for about three weeks. These formulations include in addition to the active substance or substances, conventional excipient, vehicle, binder-,preservative, etc., as called for by accepted pharmaceutical practice.

The following examples are specific embodiments of this invention. All temperatures are expressed on the Centigrade scale.

EXAMPLE 1 l-(4-Fluorophenyl)-4-[2,3,3a,4,6,7-hexahydro-2- methyl-3-phenyl-7-( phenylmethylene )-5H- pyrazolo[4,3-c]pyridin-5-yl]- l -butanone, hydrochloride 1:1

a) 3,5-Bis(phenylmethylene)-4-piperidinone, hydrochloride 14 g. (0.1 mole) of N-acety1-4-piperidinone and 32 g. (0.3 mole) of benzaldehyde, 33 ml. of concentrated HCl and m1. of ethanol are refluxed together. A solid separates after approximately 45 minutes of refluxing. Refluxing is continued for a total of 6 hours, and the mixture is kept overnight at room temperature. The light yellow solid is filtered, washed with ethanol then with ether and air dried to yield 26 g. of 3,5-bis(- phenylmethylene)-4-piperidinone hydrochloride; m.p. 273-275. b. 3,3a,4,5,6,7-Hexahydro-2-methyl-3-phenyl-7- (phenylmethylene)-2H-pyrazolo[4,3-c]pyridine 9.5 g. (0.03 mole) of the 3,5-bis(phenylmethylene)- 4-piperidinone, hydrochloride from part (a) and 1.5 g. (0.03 mole) of methylhydrazine in 200 ml. of methanol are heated and the resulting solution is refluxed for 4 hours. The solvent is removed on a rotary evaporator to heave a solid residue which on trituration with ether and cooling gives 9.5 g. of crude product; m.p. 2l0-2l2. Crystallization from 250 ml. of ethanol yields 6.0 g. of light yellow 3,321.4,5,6,7-hexahydro-2- methyl-3-phenyl-7-(phenylmethylene)-2H- pyrazolo[4,3-c]pyridine, hydrochloride; m.p. 2l8220. The hydrochloride salt is treated with K CO to yield the free base.

0. l-( 4-Fluorophenyl )-4-[ 2,3,3a,4,6,7-hexahydro-2- methyl-3-phenyl-7-(phenylmethylene)-5H- pyrazolo[4,3-c]pyridin-5-yl]-l-butanone, ride (l:l)

A mixture of 7.0 g. (0.023 mole) of 3,3a,4,5,6,7-hexahydro-2-methyl-3-phenyl-7-( phenylmethylene )-2I-I- pyrazolo-[4,3-c]pyridine from part (b), 6.0 g. (0.03 mole) of 4-chloro-l-(4-fluorophenyl)-l-butanone, 6.0 g. (0.057 mole) of pulverized Na CO and 75 ml. of dimethylformamide is stirred and refluxed for hours. The bulk of the dimethylformamide is removed on a rotary evaporator at 2 mm. and the cooled residue is shaken with 100 ml. of CHCl and 50 ml. of water. The layers are separated and the aqueous phase is extracted with CHC1 (2 X 50 ml.). The combined CHCL, layers are washed with water (3 X 50 ml.), dried (MgSO and the solvent evaporated to give 13.2 g. of a reddish oil. This oil is taken up in 100 ml. of methyl ethyl ketone and treated with 3.9 ml. of 6.0 N alcoholic HCl. The methyl ethyl ketone liquor is poured into 700 ml. of stirred ether to precipitate a solid which is filtered under N washed with ether, and dried in vacuo to yield 4.9 g. of residue; m.p. l2l-l25 (foaming); s. 80. This residue is stirred with ml. of isopropyl alcohol, and after cooling overnight, the insoluble solid is filtered, washed with isopropyl alcohol and ether, and dried in vacuo to yield 1.1 g. of crude product; m.p. l75-l78. Crystallization from 7 ml. methanol 70 ml. ether yields 0.9 g. of light yellow solid l-(4-fluorophenyl)-4-[2,3,3a,4,6,7-hexahydro-2-methyl-3-phenyl- 7-(phenylmethylene )-5H-pyrazolo[4,3-c ]pyridin-5- yl]-l-butanone, hydrochloride (1:1); m.p. l80l82.

EXAMPLE 2 l-( 4-Fluorophenyl )-4-[2,3 .3a,4,6,7-hexahydro-3-phenyl- 7-( phenylmethylene 5 H-pyrazolo 4,3-c ]pyridin- 5-yl]- l -butanone, hydrochloride hydrochlo- Following the procedure of example 1 but substituting hydrazine for the methylhydrazine in part (b), one obtains l-(4-fluorophenyl)-4-[2,3,3a,4,6,7-hexahydro- 3-phenyl-7-( phenylmethylene )-5I-I-pyrazolo[4,3- cjpyridin-5-yl1- l butanone hydrochloride.

EXAMPLES 3-23 Following the procedure of example 1 but employing the appropriate substituted benzaldehyde in part (a) and the appropriate hydrazine in part (b) one obtains the following compounds of formula II shown in C01. A which are converted to the products of formula I show in Col. B.

Col. A

' R N-N/ I i X Also by varying the procedure of part (a) of example 1 as explained above one can obtain compounds wherein X and X are different.

EXAMPLES 24-55 -continued CoLA Col. B Co]. A (301- B Cl- CH. "-R Cl-(CH ),,CR

O I l m (en c R (CH C-R 2 n g Ex. n R Ex. n R

24 1 CH. 25 1 c n. 8 I Q 26 l 7 27 I :--C,H 28 2 C- H.-, Z0 29 2 n c.H., 5 .10 3 CH 49 3 3| 3 nC;,H 32 4 CH;; 33 4 (3H,,

50 3 Q 15 L 35 1 G C1 4 ill F 36 I G G GHQ 53 l Additionally. by reacting the compounds of Col. A in examples 24 to 55 with the compounds of Col. A in 41 3 Q examples 3 to 23, other compounds within the scope of 3 the invention are obtained. 2 4 EXAMPLE 56 4-[2.3.3a,4,6.7-Hexahydro-2-methyl3-phenyl-7- 43 4 O F (phenylmethylene)-5H-pyraz0lo[ 4.3-c ]pyridin-5-y] 1- Z-butanone. hydrochloride (1:1)

A stirred solution of 6.0 g. (0.02 mole) of I Q 3.3a,4,5.6.7-hexahydro-2-methyl-3-phenyl-7-(phenyl- N methylene)-2H-pyrazolo-[4,3-0]pyridine from examg 1 ple l(b) in 60 ml. of dimethylformamide is treated with 60 1.9 ml. (0.022 mole) of 98.5 percent 3-buten-2-one and kept overnight at room temperature. The solution N is then poured into 600 ml. of cold water and the oily 46 3 product is extracted with ether (5 X 100 ml). The combined extracts are washed with water (3 X 100 ml.). dried (MgSO and the solvent evaporated to 47 4 give 7.3 g. of light yellow glass-like base. This base is dissolved in 40 ml. of acetonitrile, treated with 3.3 ml. of 6.0 N HCl, and diluted to 200 ml. with ether. The

9 HCl salt separates initiallyv as an oil, but on rubbing crystals appear. The material is allowed to crystallize at room temperature for several hours and then is cooled overnight to yield 7.4 g. of crude product; mp. 181183 (dec.). Crystallization from a mixture of 80 ml. of warm methanol and 400 ml. of ether (solution initially) yields 5.2 g. of light yellow solid 4-[2,3,3a- 4,6,7-hexahydro-2-methyl-3-phenyl-7-(phenylmethylene )-H-pyrazolo[4,3-c]pyridin-5-yl -2-butanone, hydrochloride (1:1); m.p. l85l87 (dec.).

EXAMPLE 57 3-[2,3,3a,4,6,7-Hexahydro-2-methyl-3-phenyl-7- (phenylmethylene)-5H-pyrazolo[4,3-c]pyridin-5-yl]- l-phenyl- 1 -propanone. hydrochloride l: 1

A stirred mixture of 5.0 g. (0.0165 mole) of 3,3a,4,5,6,7-hexahydro-2-methyl-3-phenyl-7-(phenylmethylene )-2l-l-pyrazolo[4,3-c]pyridine from example 1(b) and 3.6 g. (0.0168 mole) of 3-(dimethylamino)-lphenyl-l-propanoneHCl in 100 ml. of ethanol is heated and the resulting solution is refluxed for six hours. The ethanol is allowed to distill off gradually into a Dean-Stark tube to help remove by-product, dimethylamine, while fresh solvent is added intermittently through an additional funnel to maintain the" volume at approximately 100 ml. After standing overnight at room temperature, the bulk of the ethanol is removed on a rotary evaporator to give a gummy residue which is shaken with 250 ml. of ether. A portion of the residue dissolves leaving some solid undissolved. The undissolved portion is filtered, washed with ether, and dried in vacuo to yield 2.9 g. The ether filtrate is evaporated to give 5.9 g. of a light yellow foamy residue which is redissolved in 250 ml. of ether, stirred, and treated with alcoholic HCl until no more solid separates. This solid material is filtered under N washed with ether, and dried in vacuo to yield 6.4 g. which is combined with the 2.9 g. previously obtained and then stirred for one hour with 75 ml. of water, filtered, washed with water, and air dried to yield 5.1 g. of crude pale .yellow product; m.p. l75l77 (dec.). Crystallization from 200 ml. of ethanol yields 3.8 g. of colorless 3-[2,3,3a.4,6,7-hexahydro-2-methyl-3-phenyl-7- (phenylmethylene)-5H-pyrazolol[4,3-c]pyridin-5-yl]- 1-phenyl-1-propanone, hydrochloride (1:1); m.p. 182184 (dec.).

EXAMPLES 58-66 Following the procedure of example 56 or 57 but employing the vinyl ketone shown below in Col. A one obtains the final products shown in C01. B.

A Col B -continued CoLA Col. B ll CH=CHCR 1 l I H 1 8 1 (CH2) 2-CR Ex. R'

n i v 6| t-C,H,,

Similarly by employing the compounds shown in C01. A of examples 3 to 23 in the procedure of examples 56 to 66, other compounds within the scope of the invention are prepared.

EXAMPLE 67 l-( 4-Fluorophenyl )-4- 2-acetyl-2,3 ,3a,4,6,7-hexahydro-3-ph enyl-7-( phenylmethylene )-5 H-pyrazolo 4, 3- c ]pyridin-S-yl l -butanone, hydrochloride A mixture of 10 g. of l-(4-fluorophenyl)-4- [2,3,3a,4,6,7-hexahydro-3-phenyl-7-(phenylmethylene 5H-pyrazolo[4,3-c]pyridin-5-yl1- l-butanone, hydrochloride from example 2 and 250 ml. of acetic anhydride is refluxed for four hours. The solution is concentrated on a rotary evaporator and the residue is cooled and triturated with ether to yield l-(4-fluorophenyl )-4-[ 2-acetyl-2,3 ,3a,4,6,7-hexahydro-3-phenyl- 7-( pheny lmethylene )-5 H-pyrazolo[ 4, 3-c pyridin-S- yl]-1-butanone, hydrochloride.

Similarly, by employing the substituted benzaldehydes from examples 3 to 23 or the compounds from Col. A of examples 24 to 55 or other acylating agents such as propionyl chloride in the procedures of example 2 and example 67, other compounds within the scope of the invention are obtained.

EXAMPLE 68 3-[ 2,3 ,3a,4,6,7-Hexahydro-2-methyl-3-phenyl-7- (phenylmethylene)-5H-pyrazolo[4,3-c]pyridin-5-yl]- l-phenyll -propanone, N-oxide The hydrochloride salt of example 57 is basified by treatment with K CO A solution of the free base in ethanol is then treated with two equivalents of 30 per- 1 1 cent H The solution is allowed to stand for two days and the solvent is removed under reduced pressure to give 3-[2,3.3a,4,6,7-hexahydro-2-methyl-3-phenyl-7- (phenylmethylene)-H-pyrazolo[4,3-c]pyridin-5-yl]- l-phenyll -propanone, N-oxide.

EXAMPLE 69 3-[ 2,3,3a,4.6,7-l-lexahydro-2-methyl-3-phenyl-7- (phenylmethylene )-5H-pyrazolo[4,3-c]pyridin-5-yl]- l-phenyll -propanone, methochloride The hydrochloride salt of example 57 is basified by treatment with K CO A solution of the free base in acetonitrile is cooled and treated with methylchloride. The solution is allowed to stand for one day and the solvent is evaporated to give 3-[2,3,3a,4,6.7-hexahydro-2-methyl-3-phenyl-7-( phenylmethylene )-5l-lpyrazolo[4,3-c]pyridin-5-yl]- l-phenyll -propanone. methochloride.

Similarly the compounds of any of examples 1 to 56 or 58 to 67 can be treated according to the procedures of example 68 or 69 to obtain the N-oxide or quaternary ammonium salt of other compounds within the scope of this invention.

EXAMPLE 70 The following is a cream formulation which is applied topically to the skin to treat dermatophytosis.

wherein R is selected from the group consisting of alkyl of l to 4 carbons,

pyridyl, thienyl, and furyl; R is selected from the group consisting of hydrogen, alkyl of l to 4 carbons, hydroxy-alkyl of l to 4 carbons, alkanoyl of 2 to 5 carbons. and

Q-alkyl 3 R is selected from the group consisting of hydrogen. alkyl of l to 4 carbons, and benzyl; X, X, and X are independently selected from the group consisting of hydrogen, Cl, F, CF CH and OCH;;.

3. The compound of claim 2 wherein R is alkyl of l to 4 carbons and X and X are the same.

4. The compound of claim 3 wherein R is methyl, R is selected from the group consisting of methyl and X and X are the same and are selected from the group consisting of hydrogen, Cl, and F; X is selected from the group consisting of hydrogen, F, and Cl; 11 is 2 or 3.

5. The compound of claim 4 wherein X and X are both hydrogen.

6. The compound of claim 5 having the name 4- [2,3,3a,4,6,7-hexahydro-2-methyl-3-phenyl-7-(phenylmethylene)-5l-l-pyrazolo[4,3c]pyridin-5-yl]-2-butanone, hydrochloride 1:1

7. The compound of claim 5 having the name 3- [2,3,3a,4,6,7-hexahydro-2-methyl-3-phenyl-7-(phenylmethylene)-5l-l-pyrazolo[4,3-c]pyridin-5-yl]- l -phenyll-propanone, hydrochloride 1:1

8. The compound of claim 5 having the name l-(4- fluorophe nyl )-4-[2,3 ,3a,4,6,7-hexahydro-2-methyl-3- phenyl-7-(phenylmethylene)-5H-pyrazolo[4,3-c]pyridin-S-yl l-butanone, hydrochloride l :l

9. The method of preparing compounds of the formula 4;

which comprises reacting a compound of the formula with a compound of the formula halo(CH- -),,CR

(alkyl-CEO wherein R is hydrogen, alkyl of l to 4 carbons, hydroxyalkyl of l to 4 carbons, or wherein alkyl is of l to 4 carbons; halo is Cl or Br; and

R, n, X, X and X are as defined in claim 1. 3 11. The method of preparing compounds of the for- X mula N,/ R wherein alkyl of l to 3 carbons; halo 15 Cl or Br; and R, n, X, X, X and X are as defined in claim 1.

10. The method of preparing compounds of the forl C mula 15 X P|I l l X CH2CH2'C|R which comprises reacting a compound of the formula R Dr x l H wherein alkyl is of l to 4 carbons which comprises a l X compound of the formula H N H with a compound of the formula I Q l l CH2=CHC-R' 1 X (CH -C-R wherein R is hydrogen. alkyl of l to 4 carbons, by-

droxy-alkyl of l to 4 carbons, or

40 with an acylatmg agent of the formula 3@ I wherein alkyl is of l to 3 carbons; and R, n, X, X, X and X are as defined in claim 1.

UNITED STATES PATENT AND TRADEMARK oFErcE CETIFICATE 0F CORRECTIQN PATENT NO. 3,926,968 Q DATED I December 16, 1975 lNVENTOR(S) John Krapoho et a1 It is certified that error appears in the above-ruentrrreu patent and that said Letters Patent 7 are hereby corrected as shown below;

G I Col. 3, line 51, "acrylating" should read -a cylating-.

Col. 4, line 5, "wherein;" should read -wherein:-.

Col. 4, line 33 "Trichophyton, Microsporum, Epidermophyton, and Malassezia" should read --Trichophyton, Microsporum,

O Epidermophyton, and Malassezia--.

Col. 5, line 2, "heave" should read leave-.

Col. 8, line 53 "methyl3" should read -methyl-3.

Q Col. 9, line 45, "pyrazolol" should read --pyrazolo-.

Col. 12, line 34, 4,3 should read 4,3-]--.

Signed and Scaled this Third Day of August1976 1 [SEAL] Attest:

RUTH c. MASON C.MA RSHALL DANN Attesling Officer Commissioner ofParents and Trademarks O 

1. A COMPOUND OF THE FORMULA:
 2. The compound of claim 1 wherein R1 is selected from the group consisting of alkyl of 1 to 4 carbons and
 3. The compound of claim 2 wherein R is alkyl of 1 to 4 carbons and X and X1 are the same.
 4. The compound of claim 3 wherein R is methyl, R1 is selected from the group consisting of methyl and
 5. The compound of claim 4 wherein X and X1 are both hydrogen.
 6. The compound of claim 5 having the name 4-(2,3,3a,4,6,7-hexahydro-2-methyl-3-phenyl-7-(phenylmethylene)-5H -pyrazolo(4, 3c)pyridin-5-yl)-2-butanone, hydrochloride (1:1).
 7. The compound of claim 5 having the name 3-(2,3,3a,4,6,7-hexahydro-2-methyl-3-phenyl-7-(phenylmethylene)-5H -pyrazolo(4,3-c)pyridin-5-yl)-1-phenyl-1-propanone, hydrochloride (1:1).
 8. The compound of claim 5 having the name 1-(4-fluorophenyl)-4-(2,3,3a,4,6,7-hexahydro-2-methyl-3-phenyl-7 -(phenylmethylene)-5H-pyrazolo(4,3-c)pyridin-5-yl)-1-butanone, hydrochloride (1:1).
 9. The method of preparing compounds of the formula
 10. The method of preparing compounds of the formula
 11. The method of preparing compounds of the formula 